Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1- deficient mice

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dc.contributor.authorMeneses-Salas, Elsa
dc.contributor.authorGarcia-Forn, Marta
dc.contributor.authorCastany-Pladevall, Carla
dc.contributor.authorLu, Albert
dc.contributor.authorFajardo, Alba
dc.contributor.authorJosé, Jaimy
dc.contributor.authorWahba, Mohamed
dc.contributor.authorBosch, Marta
dc.contributor.authorPol, Albert
dc.contributor.authorTebar, Francesc
dc.contributor.authorKlein, Andrés
dc.contributor.authorZanlungo, Silvana
dc.contributor.authorPérez-Navarro, Esther
dc.contributor.authorGrewal, Thomas
dc.contributor.authorEnrich, Carlos
dc.contributor.authorRentero, Carles
dc.date.accessioned2020-12-22T16:21:34Z
dc.date.available2020-12-22T16:21:34Z
dc.date.issued2020
dc.descriptionCentro de Genética y Genómicaes
dc.description.abstractNiemann-Pick type C disease (NP-C) is a lysosomal storage disorder characterized by cholesterol accumulation caused by loss-of-function mutations in the Npc1 gene. NP-C disease primarily affects the brain, causing neuronal damage and affecting motor coordination. In addition, considerable liver malfunction in NP-C disease is common. Recently, we demonstrated that the depletion of annexin A6 (ANXA6), which is most abundant in the liver and involved in cholesterol transport, ameliorated cholesterol accumulation in Npc1 mutant cells. To evaluate the potential contribution of ANXA6 in the progression of NP-C disease, double-knockout mice (Npc1-/-/Anxa6-/-) were generated and examined for lifespan, neurological and hepatic functions, as well as liver histology and ultrastructure. Strikingly, lack of ANXA6 in NPC1-deficient animals did not prevent the cerebellar degeneration phenotype but further deteriorated their compromised hepatic functions and reduced lifespan. Moreover, livers of Npc1-/-/Anxa6-/- mice contained a significantly elevated number of foam cells congesting the sinusoidal space, a feature commonly associated with inflammation. We hypothesize that ANXA6 deficiency in Npc1-/- mice do not reverse neurological and motor dysfunction and it further worsens overall liver function, exacerbating hepatic failure in NP-C disease.es
dc.identifier.citationMeneses-Salas E, Garcia-Forn M, Castany-Pladevall C, Lu A, Fajardo A, Jose J, Wahba M, Bosch M, Pol A, Tebar F, Klein AD, Zanlungo S, Pérez-Navarro E, Grewal T, Enrich C, Rentero C, Lack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1-deficient mice, The American Journal of Pathology (2021)es
dc.identifier.urihttps://doi.org/10.1016/j.ajpath.2020.12.009.es
dc.identifier.urihttp://hdl.handle.net/11447/3644
dc.language.isoenes
dc.publisherElsevier Inc./ American Society for Investigative Pathologyes
dc.subjectLiver dysfunctiones
dc.subjectLifespanes
dc.subjectAnnexin A6es
dc.titleLack of Annexin A6 exacerbates liver dysfunction and reduces lifespan of NPC1- deficient micees
dc.typeArticlees

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